The Collaborative Study on the Genetics of Alcoholism (COGA) is a tightly integrated and interdisciplinary project, whose overarching goals are to understand the contributions and interactions of genetic, neurobiological, and environmental factors on risk and resilience over the developmental course of AUD, including relapse and recovery. COGA is a family-based study of large, ethnically diverse families, some densely affected by AUD, and family members have been characterized in clinical, behavioral, neuropsychological, neurophysiological, and socio-environmental domains, yielding a rich phenotypic dataset paired with a large repository of biospecimens and genomewide SNP data (GWAS) in 12,145 family members. The breadth and depth of longitudinal assessments in COGA families allow genomic analyses to be conducted within a developmental context, allowing inferences regarding genetic susceptibility and environmental malleability, which may contribute to avenues for prevention and intervention. COGA builds on the key strengths of our research achievements over the past 30 years toward our central mission, to understand the genetics of AUD and its interplay with environment. In response to RFA-AA-19-001, we propose three inter-related and inter-dependent projects (Genomics, Brain Function, Lifespan) supported by 3 essential cores (NIAAA-COGA Sharing Repository (NCSR), Data Management, and Administrative). The projects and cores harness the diverse expertise of the COGA team and the close collaboration among COGA investigators resulting in tight integration and progress toward COGA's goals. Consistent with the RFA and in keeping with COGA's research agenda, the overarching specific aims for the next five years are: Aim 1: Characterize loci, genes, polygenic risk and biological pathways underlying alcohol use and AUDs, and identify the genomic and cellular/neuronal signatures that contribute to alcohol-related phenotypes Aim 2: Advance our understanding of the longitudinal course of alcohol use and AUD, and its adverse outcomes by studying genetic and environmental factors across the lifespan Aim 3: Enhance understanding of brain functioning throughout the course of AUD and recovery, and characterize alcohol related cognitive development and decline in the context of genetic and environmental factors. COGA's multi-pronged approach, long history of productive collaboration among the investigators and commitment to data sharing, will allow us to propel the field of alcohol research towards actionable findings that can be positioned to translate science to population health and clinical care. The gestalt that arises from the integration across COGA's research modalities (genomics, brain function, lifespan) is only possible within a U10 mechanism that supports effective collaboration between researchers with diverse toolkits aimed at addressing the serious public health challenge of AUD.